Professional Documents
Culture Documents
Vitamins
Dr.Mukul Mathur
Associate Professor
Department of Pharmacology
SMS Medical College
Jaipur
Dr. Prashant Mathur
Lecturer
Apex Institute of Pharmacy
Jaipur
(8.1.2008)
CONTENTS
Introduction
Fat soluble Vitamins
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Water soluble Vitamins
Vitamin B complex
Vitamin B1
Vitamin B2
Vitamin B3
Vitamin B6
Vitamin B12
Vitamin C
Keywords
Vitamin source, physiological role, deficiency, toxicity, recommended daily allowance, therapeutic use
Introduction
Vitamins are a class of organic compounds categorized as essential nutrients for life and
maintenance of normal health. These are required in small quantity in body, thus falling
in the category of micronutrients, because body uses them without breaking down, as
happens to carbohydrate and other macronutrients.
Vitamins are essential food factors which are required for the proper utilization of the
proximate principles of food like carbohydrates, lipid and proteins. These act as cofactor
in many enzyme systems and are therefore cardinal for various body functions such as
energy production, hemopoiesis, reproduction, neurological functions, hydroxylation and
synthesis of fats, amino acids, nucleic acids and nucleoprotein. Any aberrations in these
critical mechanisms cause profound changes in the nervous system and integrity of skin,
mucous membrane, synthesis and repair of connective tissue and drug metabolism, thus
serving the needs of growth, differentiation and maintenance of normal cellular function.
In 1912, Funk described a substance that was present in rice polishing and in foods that
cured polyneuritis in birds and beriberi in humans. This substance was referred to as
vitamin because it was characterized as an amine and as a vital nutrient. Vital to
indicate that these factors are necessary for life and since earlier they are identified as
having amino groups, amine was used, but later work showed that most of them did not
contain amino groups. Thus finally e was dropped to call vitamin.
Since body is unable to synthesize them (atleast in sufficient amount) they must be
provided by food. A well balanced ordinary diet supplies the vitamin needs of a healthy
person.
Although vitamins are important nutritionally, their role has been over emphasized in
clinical practice. They are useful to correct deficiencies, if any. But taking higher doses
of vitamins will not boost up the health. Generally there is increased requirement of
vitamins in chronic diarrhea, mal-absorption, and bacterial overgrowth in intestines due
to impaired intestinal absorption of vitamins. But there are some evidences available
these days, that intake of several vitamins above the minimum daily requirement may
prevent heart disease, cancer, osteoporosis and other chronic diseases.
There are vitamins like substitutes that fail to meet all the criteria necessary to be
classified as vitamins. They still have some properties of a vitamin and, in some cases,
are present in larger amounts than vitamins. There are others that body can synthesize in
sufficient amounts to meet its needs if precursors are present; some such substances
include bioflavanoids, inositol, choline, PABA(para amino benzoic acid) & carnitine.
Retinol and carotenes are fat soluble. In ideal conditions 90% of ingested retinol & 70%
of carotenes are absorbed. Cooking, especially frying in oil improves the absorption of
carotenes. Absorbed vitamin A is stored in liver as retinyl palmitate. Zinc is required for
mobilization of retinyl palmitate to free retinol. Under normal condition a well fed person
has sufficient vitamin A reserve in liver to meet his need for 6 to 9 months or more. Free
retinol is highly active, but toxic, and is therefore transported in the blood stream in
combination with retinol-binding protein (RBP), which is produced by liver. By this
complex formation vitamin A is solublized & protected from excretion. In case of
vitamin A deficiency RBP production from liver falls.
-- 400-600 g/day
-- 1000 g/day
-- 800 g/day
-- 1000 g/day
Prevention of deficiency: Prevention may be done either by: Improvement of peoples diet, so as to ensure a regular and adequate intake of
food rich in vitamin A.
Reducing the frequency and severity of contributory factors for example Protein
Energy Malnutrition (PEM), respiratory tract infections, diarrhea, and measles.
Treatment
Deficiency of vitamin A should be treated urgently.
Generally all early symptoms can be reversed by supplementation by 200,00
IU(International unit) or 110 mg of retinal palmitate in form of capsule or
injections.
Therapeutic uses
Prophylaxis of vitamin A deficiency during infancy, pregnancy, lactation,
hepatobiliary disease, steatorrhoea.
Treatment of established vitamin A deficiency
Skin diseases like acne, psoriasis, ichthyosis
Also may be used in treatment of promyelocytic leukemia.
Interactions
Vitamin E promotes storage & utilization of retinol & decreases its toxicity.
Regular use of liquid paraffin can result in vitamin A deficiency.
Long term oral neomycin induces steatorrhoea and interferes with vitamin A
absorption.
Chronic alcohol consumption results in depletion of liver stores of vitamin A.
Hypervitaminosis A or toxicity
Excessive intake of vitamin A can lead to toxicity symptoms like anorexia,
nausea, vomiting, itching, erythema, dermatitis, hair loss, irritability, headache,
peeling of skin, loss of appetite, bleeding, drowsiness & chronic liver disease.
Acute poisoning may be seen after consumption of polar beer liver, which contain
excess vitamin A.
Vitamin D
Nutritionally important forms of vitamin D in humans are ergocalceferol (vitamin D2) &
cholecalciferol(vitamin D3) . Ergocalceferol may be derived by irradiation of the plant
sterol, ergosterol. Cholecalceferol is naturally occurring (preformed) vitamin D, found in
animal fats & fish liver oils and also derived from exposure to UV(Ultra violet) rays of
sunlight.
Vitamin D, by itself, is metabolically inactive. It undergoes endogenous transformation
into several active metabolites, first in liver and later in kidney. These metabolites are
bound to specific transport proteins and are carried to the target tissues- bone & tissues.
2. sunlight : Sun exposure is perhaps the most important source of vitamin D because
exposure to sunlight provides most humans with their vitamin D
requirement
vitamin D is synthesized by the body by action of UV rays of sunlight on
7-dehydrocholestrol, which is stored in large abundance in the skin.
Physiological role of vitamin D: The major biologic function of vitamin D is to maintain
normal blood levels of calcium and phosphorus. By promoting calcium absorption,
vitamin D helps to form and maintain strong bones. Vitamin D also works in concert with
a number of other vitamins, minerals, and hormones to promote bone mineralization.
Without vitamin D, bones will become thin, brittle, or misshapen.
Research also suggests that vitamin D may help in maintaining a healthy immune system
and help in regulating cell growth and differentiation, the process that determines what a
cell is to become
RDA (Recommended daily allowance): The daily requirements of vitamin D are:
Adults
-- 2.5 mcg(100 IU)
Infants and children
-- 5.0 mcg(200 IU)
Pregnancy and lactation
-- 10.0 mcg(400 IU)
Deficiency: Nutrient deficiencies are usually the result of dietary inadequacy, impaired
absorption and utilization, increased requirement, or increased excretion (loss). A
deficiency of vitamin D can occur:
when usual intake is below recommended levels
when there is limited exposure to sunlight
when the kidney cannot convert vitamin D to its active form
when someone cannot adequately absorb vitamin D from the digestive tract
Vitamin D deficient diets are associated with milk allergy, lactose intolerance, and strict
vegetarianism. Infants fed with only breast milk receive insufficient amounts of vitamin
D unless they also receive appropriate levels of vitamin D supplementation
The classic vitamin D deficiency diseases are rickets and osteomalacia.
1. Rickets:
Observed in young children between ages of 6 months to 2 years.
There is reduced calcification of growing bones. Disease is characterized by
the growth failure, bone deformity, muscular hypotonia, tetany and
convulsions due to hypocalcaemia.
There is an elevated concentration of alkaline phosphate in serum.
Bony deformities include curved legs, deformed pelvis, pigeon chest etc.
Rickets is the softening and weakening of bones in children, usually because of an
extreme and prolonged vitamin D deficiency. Vitamin D is essential in promoting
absorption of calcium and phosphorus from the gastrointestinal tract, which children need
Risk factors: Children 6 to 24 months old are most at risk of rickets because they're
growing rapidly, and vitamin D, calcium and phosphorus play a major role in the growth
process. Risk factors for rickets include:
Lack of vitamin D. Breast-fed infants who don't receive supplemental vitamin D
are at increased risk of developing rickets. While exposure to sunlight could
produce the necessary amounts of vitamin D, sunburn and skin cancer are real
dangers for young children. Sunscreens also markedly decrease vitamin D
production.
Lack of calcium and phosphorus. Children who don't get enough calcium and
phosphorus in their diets are at increased risk of rickets. The availability of milk
and other products that contain these minerals make this cause a rarity for rickets
in the United States and other developed countries.
Screening and diagnosis: Your doctor or your child's doctor may diagnose rickets by:
Physical examination. Your doctor will check if the pain or tenderness is coming
directly from the bones, instead of the joints and muscles surrounding them.
Blood tests. These measure calcium and phosphorus levels to see if they're
normal.
X-rays. Your doctor may take images of affected bones to look for softening or
weakness.
Medical history. Kidney problems, celiac disease or diagnosis of a sibling with
rickets may help lead your doctor to a rickets diagnosis.
Complications: While easily treated once it's diagnosed, rickets has a severe list of
complications if left untreated. Untreated vitamin D deficiency rickets may lead to:
Delays in your child's motor skills development
Failure to grow and develop normally
Increased susceptibility to serious infections
Skeletal deformities
Chronic growth problems that can result in short stature (adults measuring less
than 5 feet tall)
Seizures
Dental defects
Management of rickets: The aim of treatment for rickets is to solve the underlying
disorder. If deficiencies in vitamin D, calcium or phosphorus are at fault, replacing
vitamin D and those minerals generally eliminates the signs and symptoms of rickets,
such as bone tenderness and muscle weakness. Improvement may occur within weeks.
Administration of 15000 mcg or 600,00 IU of vitamin D3 orally or IM (intra
muscular) induces rapid healing.
Diet should be supplemented with adequate doses of vitamin D.
Intake of vitamin D-fortified foods, including fortified breakfast cereal, orange
juice, fish and processed milk should be inreased.
Little sunlight is also recommended. But moderate exposure is the safest, and
infants under 6 months should not be exposed to direct sunlight.
2. Osteomalacia:
In adults vitamin D deficiency results in osteomalacia which occurs mainly in
women, especially during pregnancy and lactation, when requirement of vitamin D is
increased.
Factors which increase demand of Vitamin D: It can be difficult to obtain enough
vitamin D from natural food sources. For many people, consuming vitamin D fortified
foods and adequate sunlight exposure are essential for maintaining a healthy vitamin D
status. In some groups, dietary supplements may be needed to meet the daily need for
vitamin D.
1. Infants who are exclusively breastfed
2. Persons with limited sun exposure
3. Persons with greater skin melanin content
4. Persons with fat malabsorption
5. Pancreatic enzyme deficiencies which may be due to:
Crohn's Disease.
Cystic Fibrosis.
Liver disease.
Surgical
Prevention of deficiency: Prevention measures includesA) Educating people to expose regularly to sunlight
B) Periodic dosing (prophylaxis) of young children with vitamin D.
Hypervitaminosis D
o Excretion of vitamin D is negligible and hence excessive administration can lead to
toxicity.
o Symptoms may include- weakness, polyurea, intense thirst, difficulty in speaking,
confusion, weight loss, nausea, vomiting.
o Patient may lapse into coma, while cardiac arrhythmias and renal failure may occur.
These effects are due to hypercalcemia induced by increased intestinal absorption and
mobilization of calcium from bone.
o Hypokalemia and metabolic alkalosis are also associated.
Drug Interactions:
(a)Vitamin D and steroids: steroids may impair vitamin D metabolism, further
contributing to the loss of bone and development of osteoporosis associated with long
term use of steroidal medications
(b)Vitamin D and caffeine: High caffeine intake may accelerate bone loss. Caffeine
may inhibit vitamin D receptors, thus limiting absorption of vitamin D and decreasing
bone mineral density.
Current marketed preparations:
Arachitol
300,000 IU/ml & 600,000 IU/ml inj.
Ostelin forte 300,000 IU/ml & 600,000 IU/ml inj.
Calcirol
60,000 IU in 1 gm granule
Vitamin E
Vitamin E is a fat-soluble vitamin that exists in eight different forms. Each form has its
own biological activity, which is the measure of potency or functional use in the body.
Alpha-tocopherol (-tocopherol) is the name of the most active form of vitamin E in
humans. It is also a powerful biological antioxidant. Vitamin E in supplements is usually
sold as alpha-tocopheryl acetate, a form of alpha-tocopherol that protects its ability to
function as an antioxidant. The synthetic form is labeled "D, L" while the natural form is
labeled "D". The synthetic form is only half as active as the natural form.
Physiological role: Antioxidants such as vitamin E act to protect your cells against the
effects of free radicals, which are potentially damaging by-products of energy
metabolism. Free radicals can damage cells and may contribute to the development of
cardiovascular disease and cancer.
Vitamin E has also been shown to play a role in immune function, in DNA repair, and
other metabolic processes. The usual plasma level of Vitamin E in adults is between 0.8
to 1.4 mg per 100 ml.
Deficiency:
Vitamin E deficiency is usually characterized by neurological problems associated
with nerve degeneration in hands and feet.
Vitamin E deficiency may result in anemia, reticulocytosis, thrombocytopenia, and
erythrocyte metabolism
Degenerative changes in spinal cord, skeletal muscles and heart may be seen.
Who is at risk for vitamin E deficiency? Vitamin E deficiency is rare in humans. There
are three specific situations when a vitamin E deficiency is likely to occur.
1. persons who cannot absorb dietary fat due to an inability to secrete bile or with
rare disorders of fat metabolism are at risk of vitamin E deficiency;
2. individuals with rare genetic abnormalities in the alpha-tocopherol transfer
protein are at risk of vitamin E deficiency;
3. premature, very low birth weight infants (birth weights less than 1500 grams, or 3
pounds, 4 ounces) are at risk of vitamin E deficiency.
Blood levels of vitamin E may also be decreased with zinc deficiency
Therapeutic uses:
Supplemental doses in patients at risk (10-30mg/day).
G-6-PD deficiency prolonged treatment with 100mg/day increase survival time of
erythrocytes.
Acanthocytosis-100mg/week i.m. normalize fragility of erythrocytes.
Hypervitaminosis E
Cytotoxic effect on human lymphocyte.
Creatinurea and impaired wound healing may be seen.
Lethargy and loose motion as side effects may be seen.
Vitamin E can interfere with ion therapy.
Vitamin K
Vitamin K is a fat-soluble vitamin. The "K" is derived from the German word
"koagulation". Coagulation refers to blood clotting, because vitamin K is essential for the
functioning of several proteins involved in blood clotting.
Vitamin K occurs in two major forms- Plants synthesize phylloquinone, also known as
vitamin K1. Bacteria synthesize a range of vitamin K forms, using repeating 5-carbon
units in the side chain of the molecule. These forms of vitamin K are designated as
menaquinone-n (MK-n), where n stands for the number of 5-carbon units. MK-n is
collectively referred to as vitamin K2.
Vitamin K is a necessary participant in synthesis of several proteins that mediate both
coagulation and anticoagulation. Vitamin K deficiency is manifested as a tendency to
bleed excessively.The daily requirement of vtamin K for an adult man is about 0.03
mg/kg.
carboxylation does not occur and the proteins that are synthesized are biologically
inactive.
What essential function do gamma-carboxyglutamic acid residues endow upon a protein?
There appear to be two major effects:
First, they enable the protein to bind to membrane surfaces. Much of blood
clotting is a result of blood-clotting proteins assembling into a complex on the
membranes of platelets and endothelial cells; within these complexes, the factors
can efficiently contact one another to become activated and participate in clot
formation. Additionally, calcium is necessary for the blood clotting reaction. The
proposed mechanism involving carboxylation is that gamma-carboxyglutamic
acid residues strongly chelate calcium, and positively-charged calcium forms ion
bridges to negatively-charged phosphate head groups of membrane phospholipids.
Second, gamma-carboxyglutamic acid groups appear to participate in forming the
necessary structure of such proteins by forming calcium-mediated intrachain
interactions that link two gamma-carboxyglutamic acids to a calcium ion (similar
to disulfide bridges, but much shorter).
In infants, vitamin K deficiency may result in life-threatening bleeding within the skull
(intracranial hemorrhage)
Current marketed preparations:
Vitamin K, 10mg/ml inj.
Synkavit, 5 mg tab, 10mg/ml inj.
Kapilin,10 mg tab.
Acetomenadiones, 5, 10 mg tab
Vitamin B1 (Thiamine)
Vitamin B2 (Riboflavin)
Vitamin B3 (Niacin)
Vitamin B6 (Pyridoxine)
Vitamin B12 (Cyanocobalamine)
Vitamin B1 (Thiamine)
Thiamine exists in tissues, mostly in the form of thiamine pyrophosphate (TPP), also
known as carboxylase. It is required for the synthesis of acetylcholine.
Deficiency of Thiamine: The two principle deficiency diseases are beri beri and
wernicks encephalopathy.
Beri-beri: it may be either- dry or wet.
a. Dry Beriberi- characterized by neurological symptoms like Polyneuritis with
numbness, tingling, hyperesthesia, muscular weakness and atrophy resulting in wrist
drop, foot drop, mental changes, poor memory, loss of appetite and constipation is
seen.
b. Wet Beriberi- Characterized by cardiovascular symptoms. Palpitations,
breathlessness, high output cardiac failure and ECG changes may be seen.
Wernicks encephalopathy: - occasionally seen, often in alcoholics, characterized by
ophthalomoplegia, polyneuritis, ataxia and mental deterioration.
Management: Beriberi is treated with 10 mg of thiamine per day orally. In a case of
cardiac failure parentral thiamine is used.
Vitamin B2 (Riboflavin)
Riboflavin was the first B complex component to be isolated in pure state. It is
synthesized by all green plants and most microorganisms. It is synthesized in the human
body by the intestinal flora and is easily absorbed, although very small quantities are
stored, so there is a constant need for this vitamin. It is absorbed from small intestine
through portal vein and is passed to all tissue by general circulation.
Sources:
Richest natural source are milk, eggs, liver, kidney and green leafy vegetables.
Meat and fish contain small amounts.
Cereals and pulses also contain smaller amounts, but germination increases the
riboflavin contents.
Physiological role: It is required by the body to use oxygen and the metabolism of amino
acids, fatty acids, and carbohydrates. Riboflavin is further needed to activate vitamin B6
(pyridoxine), helps to create niacin and assists the adrenal gland. It may be used for red
blood cell formation, antibody production, cell respiration, and growth.
It eases watery eye fatigue and may be helpful in the prevention and treatment of
cataracts. Vitamin B2 is required for the integrity of the mucus membranes in the
digestive tract and helps with the absorption of iron and vitamin B6. Although it is needed
for periods of rapid growth, it is also needed when protein intake is high, and is most
beneficial to the skin, hair and nails.
Deficiency of Riboflavin: A shortage of this vitamin may manifest itself as cracks and
sores at the corners of the mouth, eye disorders, inflammation of the mouth and tongue,
and skin lesions.
Dermatitis, dizziness, hair loss, insomnia, light sensitivity, poor digestion, retarded
growth, and slow mental responses have also been reported. Burning feet can also be
indicative of a shortage.
RDA (Recommended daily allowance): Male 1- 6 mg per day and female 1.2 mg per
day although 50 mg is mostly recommended for supplementation.
Vitamin B2 Toxicity: The limited capacity to absorb orally administered riboflavin
precludes its potential for harm. Riboflavin intake of many times the RDA is without
demonstrable toxicity. A normal yellow discoloration of the urine is seen with an
increased intake of this vitamin - but it is normal and harmless.
Vitamin B3 (Niacin)
Niacin also called nicotinic acid, niacinamide or nicotinic acid and referred to as vitamin
B 3, which can be manufactured by the body. Niacin is derived from two compounds nicotinic acid and niacinamide. This vitamin differs from the other vitamins of B
complex group in that an essential amino acid, tryptophan serves as its precursor.
Sources:
Liver, kidney, meat, poultry, fish, legumes and groundnuts are the rich source of
niacin.
Milk is poor source, but their proteins are rich in tryptophan, which is converted in
the body in niacin.
In cereals it occurs in bound form, so usually unavailable.
Physiological role: Vitamin B3 is required for cell respiration, helps in the release of
energy and metabolism of carbohydrates, fats, and proteins, proper circulation and
healthy skin, functioning of the nervous system, and normal secretion of bile and stomach
fluids. It is used in the synthesis of sex hormones, treating schizophrenia and other mental
illnesses, and a memory-enhancer.
Nicotinic acid (but not nicotinamide) given in drug dosage improves the blood
cholesterol profile, and has been used to clear the body of organic poisons, such as
certain insecticides. People report more mental alertness when this vitamin is in sufficient
supply.
Deficiency of Niacin: A deficiency may cause pellagra, the classic niacin deficiency
disease, and is characterized by bilateral dermatitis, diarrhea, and dementia. A shortage of
niacin may be indicated with symptoms such as canker sores, depression, diarrhea,
dizziness, fatigue, halitosis, headaches, indigestion, insomnia, limb pains, loss of appetite,
low blood sugar, muscular weakness, skin eruptions, and inflammation.
RDA (Recommended daily allowance): Male 18 mg per day and female 13 mg per day
although 100 mg is mostly used in supplementation.
Vitamin B3 Toxicity:
Large doses given to lower cholesterol may produce hyperuricemia, and hepatic
abnormalities. These effects are reversed if the drug is reduced in amount or
discontinued.
Nicotinic acid, but not nicotinamide in doses larger than 200 mg causes flushing by
dilating the blood vessels, which can also cause the blood pressure to drop.
These flushes are normally harmless. Large dosages can also cause itching, elevated
blood glucose, peptic ulcers and liver damage.
Vitamin B6 (Pyridoxine)
Vitamin B6, also known as pyridoxine is part of the B group vitamins and is watersoluble and is required for both mental and physical health. It exists in three forms:
Pyridoxine, pyridoxal and pyridoxamine.
Sources: It is widely distributed in food. Liver, meat, fish, yeast, cereals and legumes are
rich sources of pyridoxime.
A deficiency may also result in the raising of the level of homocysteine in the blood which in high doses can be toxic to the brain, which may be involved in Alzheimer
disease. Severe deficiency may result in pernicious anemia also called Addisonian
pernicious anemia.
Another problem that appears in deficiency is the eroding of the myelin sheath - the
fatty sheath of tissue, which insulates the nerve fibers in your body.
and enhances iron bioavailability. Ascorbic acid is a great antioxidant and helps
protect the body against pollutants.
Because vitamin C is a biological reducing agent, it is also linked to prevention of
degenerative diseases - such as cataracts, certain cancers and cardiovascular diseases.
Ascorbic acid also promotes healthy cell development, proper calcium absorption,
normal tissue growth and repair - such as healing of wounds and burns. It assists in
the prevention of blood clotting and bruising, and strengthening the walls of the
capillaries.
Vitamin C is needed for healthy gums, to help protect against infection, and assisting
with clearing up infections and is thought to enhance the immune system and help
reduce cholesterol levels, high blood pressure and preventing arteriosclerosis.
RDA (Recommended daily allowance):
Infants
-- 30 mg/day
Premature babies
-- 40 mg/day
Adult male
-- 60 mg/day
Pregnant & lactating women -- 75-90 mg/day
Deficiency of vitamin C: When there is a shortage of vitamin C, various problems can
arise, although scurvy is the only disease clinically treated with vitamin C. However, a
shortage of vitamin C may result in "pinpoint" hemorrhages under the skin and a
tendency to bruise easily, poor wound healing, soft and spongy bleeding gums and loose
teeth.
Edema (water retention) also happens with a shortage of vitamin C, and weakness, a lack
of energy, poor digestion, painful joints and bronchial infection and colds are also
indicative of an under-supply
Deficiency treatment: Ascorbic acid 100-300 mg/day provides quick relief.
Therapeutic uses:
Treatment of scurvy- 0.5-1.5 g/day.
Postoperatively 500 mg/day.
Anemia: Ascorbic acid enhances iron absorption.
Vitamin C Toxicity: Excess is eliminated mostly through urine. If extremely large
amounts are taken gastrointestinal problems may appear, but will normalize when the
intake is cut or reduced. To determine a level where a person might experience
discomfort is difficult, since some people can easily stomach up to 25,000 mg per day,
while others start having a problem at 600 or 1,000 mg.
Some people using mega dose therapy of vitamin C may have side effects such as
gastrointestinal complaints including diarrhea, nausea and abdominal cramps. These side
effects normally stop as soon as high potency intake is reduced or stopped.